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This article contains information related to a recent study “Selective screening for detection of mucopolysaccharidoses (MPS) in Malaysia; A Two-year Study” Affandi et al., 2019. Any patient registered under government healthcare facilities in Malaysia and fit at least two inclusion criteria were included in this selective screening. Urine and blood from these high risk patients were obtained and analysed for glycosaminoglycans (GAGs) level before characterization using high resolution electrophoresis (HRE). Thereafter, enzyme assay for different types of MPS based on result of HRE were determined using specific substrate. Demographic data as well as laboratory findings were tabulated and analysed. The data of this study demonstrate between clinical presentation and laboratory findings among high risk patients of MPS and can be employed to improve diagnosis of MPS.

Introduction: Mucopolysaccharidoses (MPS) are a group of inherited disorders caused by the deficiency of a specific lysosomal enzyme involved in glycosaminoglycans (GAGs) degradation. This enzyme deficiency leads to accumulation of GAGs in the lysosomes, resulting in organ dysfunction and enlargement. We aimed to detect cases of MPS in patients with suggestive signs and symptoms. Methods: This was a 2-year cross-sectional study conducted during June 2014 to May 2016. Urine and whole blood samples were taken from high-risk MPS patients. All urine samples were analysed for GAGs and characterised by high resolution electrophoresis (HRE). Whole blood was collected in ethylenediaminetetraacetic acid (EDTA) tube and analysed for specific enzymes based on the clinical history and HRE findings. Results: From the 60 samples tested, 15 were positive for MPS; (Type I = 1), (Type II = 4), (Type IIIA = 3), (Type IVA = 1), (Type VI = 6). The overall prevalence of MPS among high-risk Malaysian patients was 26% (95% CI 14.72% to 37.86%). One patient had mucolipidosis. The mean age of patients when diagnosed was 5 years old. Patients with MPS were more likely to present with hepatosplenomegaly compared to other symptoms (OR = 0.974, p

Abstract The concurrent activation and surface modification (CAM) process is an integrated process used to synthesise palm kernel shell derived activated carbon (PKSdAC) in this study. CAM involves chemical activation and surface modification via metal impregnation in one process. This study investigated the usage of different acids as chemical activators and different soaking procedures for impregnating barium (Ba) in CAM-PKSdAC. It shows that chemical impregnation of PKS using 10% sulphuric acid (H2SO4) mass loading via two soaking steps can impregnate a high Ba amount of 0.86–2.98 wt. % in CAM-PKSdAC, compared to one soaking step. The two soaking steps procedure reduced the overage formation of BaSO4 from sealing the pores of PKS. Comparing HCl and H2SO4, at 30% acid mass loading, the impregnation of PKS with H2SO4 produced a higher impregnated Ba amount in CAM-PKSdAC. BaSO4 generated from the reaction between H2SO4 on the PKS surface with BaCl2 solution causes a reduction reaction at high temperatures. BaSO4 reacted with a carbon-reducing agent and is reduced to barium sulphide (BaS), impregnating Ba on CAM-PKSdAC. In conclusion, H2SO4 was found to be the suitable chemical activator with two soaking steps for the CAM process.

This study aims to determine the process synthesis parameter for a concurrent activation and surface modification (CAM) process to produce activated carbon (AC) from palm kernel shell (PKS). It is targeted to obtain high impregnation of metal functionalized group on the AC for adsorption of acid gas. The process uses sulphuric acid (H2SO4) and barium chloride (BaCl2) as activating agent and surface modification agent. The impregnated barium amount in AC was determined by inductively coupled plasma-optical emission spectrometry (ICP-OES) and X-ray fluorescence (XRF). This study utilized a batch process under different acid mass loading and activation temperatures. The ICP-OES analysis results showed that AC treated with 10 % H2SO4 at various activation temperatures (400-700 °C) exhibited high impregnated barium amounts ranging from 1.24 to 2.98 wt%. The XRF analysis also shows high impregnated barium amount ranging from 27.44-35.46 wt% for AC prepared at similar conditions. This manifests that lower acid mass loading ascribed to lower barium sulphate (BaSO4) formation after surface modification with BaCl2, which then facilitates porous structure development in PKS derived AC (PKSdAC) and sintering of barium metal on its surface during CAM by preventing sealing of pores by unreacted BaSO4 and barium sulphide (BaS) after washing of AC.

Techno-economic analysis (TEA) has been considered an important tool to evaluate the economic performance of industrial processes. Recently, the application of TEA has been observed to have exponential growth due to the increasing competition among businesses across various industries. Thus, this review presents a deliberate overview of TEA to inculcate the importance and relevance of TEA. To further support the aforementioned points, this review article starts with a bibliometric analysis to evaluate the applicability of TEA within the research community. Conventional TEA is widely known to be conducted via software modeling (i.e., Python, AMIS, MATLAB, Aspen HYSYS, Aspen Plus, HOMER Pro, FORTRAN, R, SysML and Microsoft Excel) without involving any correlation or optimization between the process and economic performance. Apart from that, due to the arrival of the industrial revolution (IR) 4.0, industrial processes are being revolutionized into smart industries. Thus, to retain the integrity of TEA, a similar evolution to smart industries is deemed necessary. Studies have begun to incorporate data-driven technologies (i.e., artificial intelligence (AI) and blockchain) into TEA to effectively optimize both processes and economic parameters simultaneously. With this, this review explores the integration of data-driven technologies in the TEA framework. From literature reviews, it was found that genetic algorithm (GA) is the most applied data-driven technology in TEA, while the applications of blockchain, machine learning (ML), and artificial neural network (ANN) in TEA are still considerably scarce. Not to mention other advanced technologies, such as cyber-physical systems (CPS), IoT, cloud computing, big data analytics, digital twin (DT), and metaverse are yet to be incorporated into the existing TEA. The inclusion of set-up costs for the aforementioned technologies is also crucial for accurate TEA representation of smart industries deployment. Overall, this review serves as a reference note for future process engineers and industry stakeholders who wish to perform relevant TEA, which is capable to cover the new state-of-art elements under the new modern era.

Background. Glycogen storage disease type 1a (GSD1a) is a rare autosomal recessive metabolic disorder characterized by hypoglycaemia, growth retardation, lactic acidosis, hepatomegaly, hyperlipidemia, and nephromegaly. GSD1a is caused by a mutation in the G6PC gene encoding glucose-6-phosphatase (G6Pase); an enzyme that catalyses the hydrolysis of glucose-6-phosphate (G6P) to phosphate and glucose. Objective. To elaborate on the clinical findings, biochemical data, molecular genetic analysis, and short-term prognosis of 13 GSD1a patients in Malaysia. Methods. The information about 13 clinically classified GSD1a patients was retrospectively studied. The G6PC mutation analysis was performed by PCR-DNA sequencing. Results. Patients were presented with hepatomegaly (92%), hypoglycaemia (38%), poor weight gain (23%), and short stature (15%). Mutation analysis revealed nine heterozygous mutations; eight previously reported mutations (c.155 A > T, c.209 G > A, c.226 A > T, c.248 G > A, c.648 G > T, c.706 T > A, c.1022 T > A, c.262delG) and a novel mutation (c.325 T > C). The most common mutation found in Malaysian patients was c.648 G > T in ten patients (77%) of mostly Malay ethnicity, followed by c.248 G > A in 4 patients of Chinese ethnicity (30%). A novel missense mutation (c.325 T > C) was predicted to be disease-causing by various in silico software. Conclusions. The establishment of G6PC molecular genetic testing will enable the detection of presymptomatic patients, assisting in genetic counselling while avoiding the invasive methods of liver biopsy.

Abstract Background Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage disease due to N-acetylgalactosamine-6-sulfatase (GALNS) deficiency. It results in accumulation of the glycosaminoglycans, keratan sulfate and chondroitin-6-sulfate, leading to skeletal and other systemic impairments. Data on MPS IVA in Asian populations are scarce. Methods This is a multicentre descriptive case series of 21 patients comprising all MPS IVA patients in Malaysia. Mutational analysis was performed by PCR and Sanger sequencing of the GALNS gene in 17 patients. Results The patients (15 females and 6 males) had a mean age (± SD) of 15.5 (± 8.1) years. Mean age at symptom onset was 2.6 (± 2.1) years and at confirmed diagnosis was 6.9 (± 4.5) years. The study cohort included patients from all the main ethnic groups in Malaysia – 57% Malay, 29% Chinese and 14% Indian. Common presenting symptoms included pectus carinatum (57%) and genu valgum (43%). Eight patients (38%) had undergone surgery, most commonly knee surgeries (29%) and cervical spine decompression (24%). Patients had limited endurance with lower mean walking distances with increasing age. GALNS gene analysis identified 18 distinct mutations comprising 13 missense, three nonsense, one small deletion and one splice site mutation. Of these, eight were novel mutations (Tyr133Ser, Glu158Valfs*12, Gly168*, Gly168Val, Trp184*, Leu271Pro, Glu320Lys, Leu508Pro). Mutations in exons 1, 5 and 9 accounted for 51% of the mutant alleles identified. Conclusions All the MPS IVA patients in this study had clinical impairments. A better understanding of the natural history and the clinical and genetic spectrum of MPS IVA in this population may assist early diagnosis, improve management and permit timely genetic counselling and prenatal diagnosis.

Background: Fructose-1,6-bisphosphatase (FBPase) deficiency is a rare autosomal recessive inborn error of gluconeogenesis. We reported the clinical findings and molecular genetic data in seven Malaysian patients with FBPase deficiency. Methods: All patients diagnosed with FBPase deficiency from 2010 to 2015 were included in this study. Their clinical and laboratory data were collected retrospectively. Results: All the patients presented with recurrent episodes of hypoglycemia, metabolic acidosis, hyperlactacidemia and hepatomegaly. All of them had the first metabolic decompensation prior to 2 years old. The common triggering factors were vomiting and infection. Biallelic mutations in FBP1 gene (MIM*611570) were identified in all seven patients confirming the diagnosis of FBPase deficiency. In four patients, genetic study was prompted by detection of glycerol or glycerol-3-phosphate in urine organic acids analysis. One patient also had pseudo-hypertriglyceridemia. Seven different mutations were identified in FBP1, among them four mutations were new: three point deletions (c.392delT, c.603delG and c.704delC) and one splice site mutation (c.568-2A > C). All four new mutations were predicted to be damaging by in silico analysis. One patient presented in the neonatal period and succumbed due to sepsis and multi-organ failure. Among six survivors (current age ranged from 4 to 27 years), four have normal growth and cognitive development. One patient had short stature and another had neurological deficit following status epilepticus due to profound hypoglycemia. Conclusion: FBPase deficiency needs to be considered in any children with recurrent hypoglycemia and metabolic acidosis. Our study expands the spectrum of FBP1 gene mutations. Key Words: Fructose-1,6-bisphosphatase, FBPase deficiency, FBP1 gene mutation

Argininosuccinate lyase (ASL) deficiency impairs the function of the urea cycle that detoxifies blood ammonia in the body. Mutation that occurs in the ASL gene is the cause of occurrence of ASL deficiency (ASLD). This deficiency causes hyperammonemia, hepatopathy and neurodevelopmental delay in patients. In this study, the clinical characteristics and molecular analysis of 10 ASLD patients were presented. 8 patients were associated with severe neonatal onset, while the other 2 were associated with late onset. Molecular analysis of ASL gene identified four new missense variants, which were c.778C>T, p.(Leu260Arg), c.1340G>C, p.(Ser447Thr), c.436C>G, p.(Arg146Gly) and c.595C>G, p.(Leu199Val) and four reported missense variants, which were c.638G>A, p.(Arg213Gln); c.556C>T, p.(Arg186Trp), c.578G>A, p.(Arg193Gln) and c.436C>G, p.(Arg146Trp). In silico servers predicted all new and reported variants as disease-causing. Structural examination exhibited that all pathogenic variants affected the stability of the tetrameric ASL structure by disturbing the bonding pattern with the neighboring residues. Conclusion: This study revealed the genetic heterogeneity among Malaysian ASL patients. This study has also expanded the mutational spectrum of the ASL. Keywords: Argininosucinate lyase deficiency, ASLD, Autosomal recessive, Mutation, Hyperammonemia

The recycle and reuse of template in MCM-41 synthesis were analysed using 23 full factorial design in order to study the effect of the template extraction parameters on the mass of MCM-41 powder produced. Four consecutive MCM-41 synthesis cycles utilizing the recycled template were studied with three factors that are ethanol fraction (A), amount of ion exchange agent (B) and the type of ion exchange agent (C). The significant effects contributed by the factors A, B and C and their interactions were identified through the half-normal probability plot and normal probability plot of the residuals. F-test and t-test were carried out to test the contribution of regression coefficients for synthesis cycles of MCM-41 synthesis models. AB interaction showed that larger mass of MCM-41 powder was obtained at high ethanol volume fraction and high quantity of ion exchange agent when either type of ion exchange agent was used.